Type IIa RPTPs and Glycans: Roles in Axon Regeneration and Synaptogenesis

Type IIa receptor tyrosine phosphatases (RPTPs) play pivotal roles in neuronal network formation. It is emerging that the interactions of RPTPs with glycans, i.e., chondroitin sulfate (CS) and heparan sulfate (HS), are critical for their functions. We highlight here the significance of these interactions in axon regeneration and synaptogenesis. For example, PTP sigma, a member of type Ha RPTPs, on axon terminals is monomerized and activated by the extracellular CS deposited in neural injuries, dephosphorylates cortactin, disrupts autophagy flux, and consequently inhibits axon regeneration. In contrast, HS induces PTP sigma - oligomerization, suppresses PTP sigma - phosphatase activity, and promotes axon regeneration. PTP sigma - also serves as an organizer of excitatory synapses. PTP sigma and neurexin bind one another on presynapses and further bind to postsynaptic leucine-rich repeat transmembrane protein 4 (LRRTM4). Neurexin is now known as a heparan sulfate proteoglycan (HSPG), and its HS is essential for the binding between these three molecules. Another HSPG, glypican 4, binds to presynaptic PTP sigma - and postsynaptic LRRTM4 in an HS-dependent manner. Type IIa RPTPs are also involved in the formation of excitatory and inhibitory synapses by heterophilic binding to a variety of postsynaptic partners. We also discuss the important issue of possible mechanisms coordinating axon extension and synapse formation.

Automated summary

This article discusses the important roles of type IIa receptor tyrosine phosphatases (RPTPs) in neuronal network formation, emphasizing their interactions with glycans such as CS and HS in axon regeneration and synaptogenesis. It was found that CS inhibits axon regeneration while HS promotes it. Additionally, PTP sigma plays a crucial role in excitatory synapse organization and interacts with neurexin and LRRTM4 in a heparan sulfate-dependent manner.